• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
  • 同族专利
  • 引用文献
  • 法律状态
  • 优先权
    • 专利摘要:
    A process for the preparation of the N-L- alpha -aspartyl-L-phenylalanine 1-methyl ester (aspartame) which is characterized by adding phosphoric acid and a lower alkyl alcohol to the reaction mixture containing N-formyl alpha -L-aspartyl- and beta -L-aspartyl-L-phenyl-alanine methyl ester and only one of the resultant deformylated isomers, i.e. aspartame phosphate precipitates. The alpha -isomer phosphate is collected by filtration and converted to free aspartame by treatment with a base.
    公开号:SU1342423A3
    申请号:SU843743902
    申请日:1984-05-25
    公开日:1987-09-30
    发明作者:Оппичи Эрнесто；Даллатомазина Франко；Джиардино Пиетро
    申请人:Фармиталиа Карло Эрба С.П.А. (Фирма)；
    IPC主号:
    专利说明:

    This invention relates to a process for the preparation of N-L-oi-ac-partyl-b-phenylalanine methyl ester, which is used in the food industry.
    The purpose of the invention is to simplify the process.
    Simplification of the process is achieved due to the fact that there is no need
    and 40 ml of acetic acid were added 400 ml of methyl alcohol and 70.4 ml of 85% aqueous phosphoric acid.
    According to Example 1, aspartam phosphate is obtained in 90% yield.
    Example4. To a solution of 100 mg of methyl ester H-formyl-91, | -B-as-partyl-b-phenylalanine (ratio
    in the compartment of the desired product Q oi: 0-H3OMepoB 1: 1) in 160 ml dichlor 15
    20
    isomer, forming; Egos at condensation of Lr-aspartic derivatives. acid and Lp-phenylalanine, since after the cleavage of the protective group from the reaction mixture is completed, only oi precipitates. isomer (aspartaphosphic). The mild acidic hydrolysis conditions prevent peptide bond cleavage. In addition, under the conditions of implementation of the proposed method, the formation of an undesirable by-product, dicketopirazine, does not occur.
    Example 1. To a solution of 100 g of methyl ester K-formyl-01:, | -L-aspar-25 tyl-b-phenylalanine (ratio o (,: | 5-isomer 8: 2) in 160 ml of dichloroethane and 40 ml of acetic acid are added at room temperature 360 ml of methyl alcohol and 35.2 ml 85% aqueous phosphoric acid.
    The mixture is heated at 40 ° C for H and then cooled.
    Phosphate of methyl ester of c6-L-acnapethane and 40 ml of acetic acid are added at room temperature to 360 ml of methyl alcohol and 35.2 ml of 99% phosphoric acid.
    The process is carried out for 11 hours.
    Methyl ester phosphate K-b-oC-aspartyl-b-phenylalanine is obtained with an output of 75%.
    Example 5 Under the conditions of example 1 (with a ratio of (X- and p-isomers 19: 1) at 55 ° C, using aspartame-phosphate in 50% yield instead of 85% phosphoric acid, instead of 85%).
    The aspartame phosphate thus obtained is converted to free asparone there by neutralizing phosphoric acid with sodium carbonate, sodium hydroxide or ammonia in an aqueous solution, 20 (analogously to example 2).
    权利要求:
    Claims (1)
    [1]
    Invention Formula
    The method of producing methyl ester of L-L-c-aspartyl-b-phenylalanine by
    The method of producing methyl ester of L-L-c-aspartyl-b-phenylalanine
    Tyl-b-phenylalanine, which crystallizes, is collected by filtration, deforming methyl ether and dried. M-formyl-b-aspartyl-b-phenylalanine
    Yield 85% (based on N-formyl-aspartame).
    Example 2, 51 g of methyl phosphate o6-b-aspartyl-b-phenyl 40
    by treating with an acid in an aqueous-organic medium when heated with subsequent cooling, the filter, by reacting with water and neutralizing the solution with an organic base, are distinguished by the fact that, in order to simplify the process, a mixture of ob- and p-isomers of methyl
    treatment with acid in an aqueous-organic medium when heated, followed by cooling, filtering, dissolving, dissolving in water and neutralizing the solution with an organic base, is distinguished by the fact that, in order to simplify the process, a mixture of ob- and p-isomers of methyl is used
    Nina is dissolved in 300 ml of water, the pH of the resulting solution is adjusted to 5.2 with a 20% aqueous solution of sodium hydroxide, stirred
    At room temperature for 1 hour, cooling the K-formyl-L-aspartyl-L-phenyl ether and the precipitated free alanine, the condensation product of L-for-aspartame, is collected by filtration.
    27.9 g of pure compound are obtained in 73% yield, m.p. 233-235 С
    50
    (decomposition) . +33.2 (, acetic acid).
    Example To a solution of 100 g of methyl ester H-formyl-p, 5-b-aspartyl-b-phenylalanine (cI isomer ratio) in 380 ml of ethyl acetate
    mil of aspartic anhydride with L-phenylalanine methyl ester dissolved in dichloroethane or ethyl acetate, and in the presence of acetic acid, is treated with 50-99% aqueous phosphoric acid, taken in an amount of 1.2–5 mol per 1 mol of the starting product lower C, -C-alkanol 55 at 25-55 ° C.
    BNIIPI
    Order 4447/58 Circulation 347
    Random polygons pr-tie, Uzhgorod, st. Project, 4
    and 40 ml of acetic acid were added 400 ml of methyl alcohol and 70.4 ml of 85% aqueous phosphoric acid.
    According to Example 1, aspartam phosphate is obtained in 90% yield.
    Example4. To a solution of 100 mg of methyl ester H-formyl-91, | -B-as-partyl-b-phenylalanine (ratio
    ethane and 40 ml of acetic acid are added at room temperature with 360 ml of methyl alcohol and 35.2 ml of 99% phosphoric acid.
    The process is carried out for 11 hours.
    Methyl ester K-L-oC-aspartyl-L-phenylalanine phosphate is obtained in 75% yield.
    Example 5 Under the conditions of Example 1 (with a ratio of (X- and p-isomers of 19: 1) at 55 ° C, using aspartame-phosphate in 50% yield instead of 85% in phosphoric acid) is obtained.
    The aspartame-phosphate thus obtained is converted into free aspartame by neutralization of phosphoric acid with sodium carbonate, sodium hydroxide or ammonia in an aqueous solution (as in Example 2).
    Invention Formula
    The method of producing methyl ester of L-L-c-aspartyl-b-phenylalanine by
    deforming the methyl ester of M-formyl-b-aspartyl-b-phenylalanine
    0
    treatment with acid in an aqueous-organic medium when heated, followed by cooling, filtering, dissolving, dissolving in water and neutralizing the solution with an organic base, is distinguished by the fact that, in order to simplify the process, a mixture of ob- and p-isomers of methyl is used
    of K-formyl-L-aspartyl-L-phenyl-alanine ester is a condensation product of L-form-
    of K-formyl-L-aspartyl-L-phenyl-alanine ester is a condensation product of L-form-
    mil of aspartic anhydride with L-phenylalanine methyl ester dissolved in dichloroethane or ethyl acetate, and in the presence of acetic acid, is treated with 50-99% aqueous phosphoric acid, taken in an amount of 1.2–5 mol per 1 mol of the starting product and lower C, -C-alkanol at 25-55 ° C.
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    同族专利:
    公开号 | 公开日
    IL71930D0|1984-09-30|
    IE841312L|1984-11-30|
    DK270084D0|1984-05-30|
    DK163928C|1992-09-14|
    SE8402953D0|1984-05-30|
    US4656304A|1987-04-07|
    NO842129L|1984-12-03|
    NZ208279A|1987-04-30|
    ATA172384A|1988-04-15|
    PH21764A|1988-02-18|
    SE459176B|1989-06-12|
    AU561593B2|1987-05-14|
    CS257778B2|1988-06-15|
    DK163928B|1992-04-21|
    AU2876784A|1984-12-06|
    IT8421147D0|1984-05-29|
    DE3419921A1|1984-12-13|
    FI841952A|1984-12-01|
    PT78657A|1984-06-01|
    CS399884A2|1987-11-12|
    FR2547816B1|1987-10-30|
    YU44456B|1990-08-31|
    DE3419921C2|1989-04-20|
    NL192112B|1996-10-01|
    JPH0570638B2|1993-10-05|
    YU92284A|1986-10-31|
    NL192112C|1997-02-04|
    FI80465B|1990-02-28|
    ES532916A0|1985-08-01|
    ZA844071B|1984-12-24|
    IE810577L|1982-09-16|
    KR910002387B1|1991-04-20|
    JPS59227850A|1984-12-21|
    NL8401674A|1984-12-17|
    IL71930A|1986-12-31|
    GR82034B|1984-12-12|
    ES8506598A1|1985-08-01|
    IE57662B1|1993-02-24|
    IT1212097B|1989-11-08|
    PT78657B|1986-09-08|
    FR2547816A1|1984-12-28|
    GB8314907D0|1983-07-06|
    DK270084A|1984-12-01|
    SE8402953L|1984-12-01|
    NO163738B|1990-04-02|
    FI841952A0|1984-05-15|
    CH659061A5|1986-12-31|
    CA1244008A|1988-11-01|
    BE899783A|1984-09-17|
    KR850000030A|1985-02-25|
    NO163738C|1990-07-11|
    HUT34434A|1985-03-28|
    FI80465C|1990-06-11|
    HU191146B|1987-01-28|
    AT387024B|1988-11-25|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    EA000177B1|1996-04-10|1998-12-24|ХОЛЛАНД СВИТЕНЕР КОМПАНИ В.о.Ф.|METHOD FOR DEPOSITING alpha-L-ASPARTYL-L-PHENYLALANINE-METHYL ESTER ON AN EDIBLE SUPPORT|US3492131A|1966-04-18|1970-01-27|Searle & Co|Peptide sweetening agents|
    US3833553A|1970-01-31|1974-09-03|Ajinomoto Kk|Method of producing alpha-l-aspartyl-l-phenylalanine alkyl esters|
    JPS5140069B1|1971-07-09|1976-11-01|
    BE791544A|1971-11-19|1973-05-17|Stamicarbon|PREPARATION OF ALKYL ESTERS OF DIPEPTIDE|
    JPS5726505B2|1974-07-23|1982-06-04|
    JPS5726588B2|1975-08-14|1982-06-05|
    US4173562A|1976-12-27|1979-11-06|Monsanto Company|Process for the preparation of α-L-aspartyl-L-phenylalanine methyl ester|
    JPH0133479B2|1981-02-10|1989-07-13|Ajinomoto Kk|
    JPH0372640B2|1982-04-22|1991-11-19|Ajinomoto Kk|JPH0680075B2|1985-12-24|1994-10-12|味の素株式会社|Process for producing N-formyl-α-L-aspartyl-L-phenylalanine methyl ester|
    US5283357A|1988-03-14|1994-02-01|Mitsui Toatsu Chemicals, Incorporated|Separation method of α-l-aspartyl-l-phenylalanine methyl ester|
    JP2662287B2|1988-03-14|1997-10-08|三井東圧化学株式会社|Method for separating α-L-aspartyl-L-phenylalanine methyl ester|
    US5017690A|1989-08-11|1991-05-21|W. R. Grace & Co.-Conn.|Deblocking N-formyl aspartame compounds|
    NL9201408A|1992-08-05|1994-03-01|Holland Sweetener Co|Method for crystallizing aspartame.|
    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    GB838314907A|GB8314907D0|1983-05-31|1983-05-31|Aspartame synthesis|
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